Converging evidence from molecular genetics, neurophysiology, and the cognitive neurosciences continues to suggest that sleep plays an important role in the process of learning and memory formation. More specifically, studies in humans have established that learning of procedural sensory and motor skills depends explicitly on sleep for the development of additional performance gains following task acquisition, while equivalent periods of daytime (or nighttime) waking offer no such improvements. Despite these advances, there remains a complete paucity of studies focusing on the underlying neural mechanisms associated with sleep-dependent learning in the human brain. Proposed here is an experimental approach specifically designed to investigate the neural correlates of sleep-dependent human motor skill learning using functional magnetic resonance imaging (fMRI). The aims of this proposal are to (a) determine whether a post-training time period containing sleep leads to a different pattern of task-dependent neural activation, relative to a post-training time period without sleep, and (b) determine whether changes in brain activation occurring specifically across the sleep time period correlate both with overnight performance improvements and sleep-stage recordings. Subjects will therefore be trained on a motor skill task and, following an intervening time period containing either wake or sleep, will be retested while undergoing fMRI scanning. The respective patterns of task-dependent regional brain activity will then be contrasted to dissociate the contributions of each respective brain-state on motor skill learning, and correlated with overnight sleep-stage recordings. Understanding how sleep-dependent learning is manifest in brain plasticity has wide reaching practical, clinical and scientific implications, such as determining the role of sleep in developmental neuronal plasticity; in the functional reorganization of brain regions following trauma or stroke; in the potential relationship between sleep disturbances and impaired memory function in a variety of patho-physiological conditions; as well as expanding our scientific understanding of mechanisms underlying memory consolidation processes in general.